anticholinergics
Table of Contents
anti-muscarinic anticholinergic agents
Summary of anticholinergic effects:
- mydriasis, cycloplegia, tachycardia, antispasmodic GIT;
- dry mouth, decr. fasting gastric acid secretion; decr. motility;
- dilates pelves, calyces, ureters, bladder;
- delayed emptying of GB after fatty meal;
- dry, hot skin;
Side effects of anticholinergics:
- blurred vision; dry mouth; hyperthermia (esp. infants);
- constipation; urine retention; tachycardia (esp. fit young adults);
- precipitate glaucoma;
- NB. low dose may cause initial mild bradycardia;
Anticholinergic toxicity
- Overdoses of anticholinergics such as atropine are remarkably safe in ADULTS but DANGEROUS in CHILDREN!
- Children much more susceptible to toxic effects esp. hyperthermia (except tachycard.);
- Although recovery has occurred in children with 400mg, death has occurred with 2mg !!
- tachycardia with weak pulse; iris practically obliterated;
- skin flushed, hot, dry & scarlet; ataxia; restlessness; excitement;
- delirium; toxic psychoses (sometimes even from top.ophth. use!); coma;
- ie. “Dry as a bone, blind as a bat, red as a beet, mad as a hatter”
Alkaloid antimuscarinics:
-
- belladoona (Atrop spp)
- Scopolamine (l-hyoscine):
- henbane (Hyoscyamus spp)
- Used IM (0.008mg/kg) with narcotic → decr. secretions;
- may → tranquillisation & amnesia but hyperexcit. if pain;
- Used to prevent motion sickness:
- top.patches 1.5mg releasing 1mg over 72hrs, steady state @ 5hrs;
- → apply 5-6 hrs before travel! only age 10-65yrs;
- after removal, plasma [] falls over a few hours;
- must wash hands after handling else transfer to eyes
- may cause idiosync. confusional states/hallucination
- other plants:
- Datura spp (Angel's trumpet)
- Duboisia spp (Corkwood) such as D. myoporoides - used by Australian aborigines
Tertiary amine antimuscarinics:
- Homatropine hydrobromide:
- mainly use as mydriatic: 1% → peak 40-60min; return normal 1-3 days;
- 5% → full mydriasis but still not full cycloplegia;
- Cyclopentolate HCl:
- mainly as mydriatic: 0.5-1% → peak 30-60min, return normal 1 day;
- Tropicamide:
- mainly as mydriatic: 0.5-1% → peak 20-40min, return normal 6hrs;
- Dicyclomine:
- Used in peptic disease & hypermotility states;
Tertiary amine antimuscarinics with CNS activity (anti-Parkinsonian):
- Parkinsonism → decr. dopamine in striatum → inc. excitatory cholinergics there
- Benztropine (Cogentin):
- synthetic compound result f. combination active portions of both atropine & diphenhydramine → antimusc. & antihistamine actions;
- Often used to Rx oculogyric crises: 1-2mg IM then 1-2mg bd/tds oral;
- NB. because it has potent atropine-like actions care in children & note that it is C/I in <3yr olds!!
- Benzhexol (Trihexyphenidyl HCl) (Artane):
- similar activities to atropine but usually adverse effects less;
- Most commonly used anticholinergic for Parkinson's;
Quaternary ammonium antimuscarinics (less CNS effects):
- These more polar drugs have less CNS effects than atropine but in toxicity may cause significant ganglionic blockade resulting in orthostatic hypotension - this may be reversed by phenylephrine or methoxamine.
-
- lacks atropine's CNS effects & rel.lack of inhib. of ciliary beating;
- more potent bronchodilatory, dry mouth & tachycardic effects;
- M3 receptor half life 3hrs ⇒ duration action 4-6hrs, max. response at 1.5-2hrs ⇒ qid dosing
- when inhaled, little systemic effect as <1% absorbed from lungs/GIT;
- tiotropium bromide:
- structural analague of ipratropium
- M3 receptor half life 36hrs ⇒ once daily dosing
- increases FEV1 & quality of life in pts with COPD, lengthening time to 1st exacerbation & time to 1st hospital admission
- number pts needed to Rx for 1 yr to prevent:
- one exacerbation = 9 pts
- one admission = 23 pts
- propantheline:
- Once used in Rx of PU & still in Rx of some diarrhoeal conditions;
- glycopyrrolate:
- Once used in Rx of PU & still in Rx of some diarrhoeal conditions;
- sometimes used as premed. for ketamine aneasthesia to reduce secretions
- now available as long acting muscarinic antagonist inhaler (LAMA) for chronic obstructive pulmonary disease (COPD) as glycopyrronium bromide and marketed as:
- Seebri breezhaler
- Ultibro Breezhaler 110/50 (indacaterol + glycopyrronium) - introduced Aust. 2014
- aclidinium:
- long acting muscarinic antagonist inhaler (LAMA) for chronic obstructive pulmonary disease (COPD) marketed as:
- Bretais Genuair - introduced Aust. 2014
- umeclidinium:
- long acting muscarinic antagonist inhaler (LAMA) for chronic obstructive pulmonary disease (COPD) marketed as:
- Incruse Ellipta - introduced Aust. 2014
- Anoro Elipta - (vilanterol + umeclidinium)
Anti-M3 anti-muscarinics for Mx of over-active bladders:
- these are used to Rx overactive bladders, urgency and urge incontinence
- they may cause urinary retention, blurred vision, dry mouth, constipation, acute glaucoma, tachycardia, prolonged QTc, and heat illness in hot weather due to reduced perspiration
- Tolterodine tartrate:
- antimuscarinic introduced in 2005 to help Rx urinary incontinence & over-active bladder
- acts on M2 and M3 receptors but preferentially targets bladder receptors
- less side effects than oxybutynin (M3 and M1 selective and acts more on the parotids than the bladder)
- Darifenacin hydrobromide:
- antimuscarinic introduced in 2007 with more affinity for M3 receptors & thus used in Rx of over-active bladder
- Solifenacin succinate:
- antimuscarinic introduced in 2007 with more affinity for M3 receptors & thus used in Rx of over-active bladder
anticholinergics.txt · Last modified: 2019/08/02 03:45 by 127.0.0.1